This K23 application is designed to establish the candidate's independent career in patient-oriented research on the genetics of cardiac arrhythmias. The research and training plans include mentoring in molecular genetics in combination with mentoring in the psychosocial implications of genetic testing and genetic disease. Cardiovascular disease (CVD) claims more than 500,000 US lives each year. As many as 2/3 of victims of CVD die an arrhythmic death within one hour of symptom onset. Others suffer arrhythmia-related disability despite state of the art therapy. Risk stratification has included family history and lifestyle factors, but reliable indicators of risk have been elusive. Genes that confer arrhythmia susceptibility may provide the link to more accurate risk assessment. An overriding hypothesis of this proposal is that cardiac rhythm "building block" genes (e.g. ion channels) are major genetic loci for clinically significant rhythm disorders. This hypothesis challenges a commonly held tenet that the etiology of arrhythmias is genetic only if it is detected during fetal or perinatal life, and acquired only if detected considerably later. Some clinically significant cardiac arrhythmias may involve both genetic susceptibility and environmental risk factors leading to their later onset. The Specific Aims of this proposal's training plan include acquiring didactic and laboratory training in techniques used to investigate the genetics of CVD while developing a foundation for answering questions about the impact of genetic testing on CVD patients and their families. Specific Aims of the research plan are identifying genetic and environmental contributions to cardiac arrhythmias and identifying quantitative trait loci influencing development of cardiac arrhythmias and conduction block. Data will be analyzed using variance component and genome wide linkage analysis. We are attempting to uncover novel genetic risk factors with the long-term goal of providing at-risk families with future options for pre-symptomatic testing. These activities will provide the foundation for the candidate's independent research career and lead to future studies integrating molecular techniques with investigations of how predictive genetic testing affects the health and health behaviors of individuals with cardiac arrhythmias and their families. [unreadable] [unreadable]